The gingival structure that supports the teeth is composed of the gingiva, alveolar bone, periodontal membrane, and dental cementum. Inflammation that is limited to the gingival area is classified as gingivitis, whereas inflammation that spreads from the gingiva to the alveolar bone, periodontal membrane, and dental cementum is classified as periodontitis. The treatment of gingivitis and more advanced periodontitis requires the removal of dental stains such as dental plaque and dental calculus, and the elimination of the cause of gingival swelling, if any, due to drug or pregnancy-induced endocrine stimulation. Effective methods include treatment with aminocaproic acid, which has anti-inflammatory action and anti-plasmin action on gingivitis and periodontitis, to inhibit the onset of such symptoms; the use of minocycline hydrochloride to eradicate tetracycline-resistant staphylococcus, which is a pathogen of periodontal inflammation; and the macrolide antibiotic, erythromycin, for the treatment of biofilm and pathogens in periodontal pockets. 60% of the periodontal tissue is composed of collagen. Continued collagen degeneration leads to gingival shrinkage and recession. The group of enzymes that act on and degrade extracellular matrices such as collagen are referred to as matrix metalloproteinases (hereinafter referred to as MMP). There are at least 10 types of MMP, among which collagenase is reportedly expressed around the attachment epithelia of the periodontal tissue and the periodontal pocket epithelia (see Non-Patent Document 1). It has also been reported that gelatinase is produced by epithelial cells through stimulation by periodontal pathogen-derived lipopolysaccharides and the like, and degrades type IV collagen, which is a constituent of the basement membrane. This shows that elevated MMP activity is intimately related to the progression of periodontal diseases. Normal individuals reportedly have lower levels of MMP than patients with gingivitis or periodontitis (see Non-Patent Document 2). Improvement of symptoms by treating periodontal diseases has also been reported to result in lower MMP activity (see Non-Patent Document 3). Agents for inhibiting the spread of gingival epithelial cells which contain plant extracts such as red grape, rosemary, ginkgo, St. John's wort, and alum are thus available to inhibit MMP activity and production (Patent Document 1). However, the above treatments currently do not afford adequate therapeutic results, and gingivitis often progresses to periodontitis, resulting in a loss of teeth in many individuals.
The common cold is caused by a virus. No drugs are effective for colds, and the only treatment is symptomatic treatment. Pseudoephedrine which is a decongestant is available for nasal discharge and nasal obstruction in colds, but its effects are limited. Oxymetazoline or phenylephrine nasal sprays are fast-acting, but their use is limited to a few days, as prolonged use may result in chronic nasal obstruction. Antihistamines and anti-allergy medication are available for nasal discharge, but side effects include sleepiness, and these types of medication are not effective for nasal obstruction. Centrally acting codeine and dextromethorphan are available for coughing. Codeine can result in nausea, vomiting, constipation, or tolerance and physical dependence. Respiratory depression is a side effect of higher doses of dextromethorphan. Palpitations, tremors, tachycardia, head ache, and vomiting are side effects of the bronchodilators, ephedrine and theophylline, which are not very effective anyway. N-(benzoyl)amino acid derivatives have recently become available for cough (Patent Document 2), but their clinical efficacy and side effects are still known. There is thus a need for a drug that would be effective and free of side effects even when used for longer periods of time.
Steroids, bronchodilating sympathetic drugs, anti-allergic agents, IgE neutralization therapy with anti-IgE antibodies, and ubidecarenone medication are effective for bronchial asthma (see Non-Patent Document 4), while effective therapies for respiratory diseases include those that are effective for dyspnea (see Non-Patent Document 5) and that are also effective on mast cells and eosinophils, such as dihomo-γ-linolenic acid (see Non-Patent Document 4), and the cysLT1 receptor antagonists pranlukast hydrate, montelukast sodium, and zafirlukast (Patent Document 5). Steroid inhalation therapy is currently the mainstream and has been shown to be effective in preventing death by asphyxiation due to bronchial asthma. However, the course of bronchial asthma is protracted, lasting from dozens of years to a lifetime, and the side effects of steroids are a problem. There is thus a need for a fast-acting drug that would be free of side effects, that would be as effective as or more effective than steroids, and that would be capable of long-term use.
Conventional impotence therapeutics for compromised sexual sensation in the glans penis, clitoris, and vagina are primarily in the form of oral medication, and their raw materials include extract of Trionychidae or garlic, powder or extract of Agkistrodon blomhoffii or Yohimbe bark, as well as maca and the like from the South American highlands. Testosterone transdermal absorption patches (Patent Document 6) and patches composed of stimulants such as chili pepper, capsaicin, or menthol have also recently become available (Patent Document 7), but there is a need for a drug that would be free of side effects, that would enhance the degree of sexual sensation in individuals with diminished sexual sensation, and that would be capable of long-term use.
Whiteing hair, hair loss, and thinning hair are a concern to people as they age. Whiteing hair is a phenomenon of aging, in which melanocytes stop producing melanin. The active ingredients of hair growth drugs include blood circulation stimulants, local stimulants, follicle activators, antiandrogens, antiseborrheics, keratolytics, bactericides, anti-inflammatories, and the like. Hair also repeatedly grows and falls out according to hair growth cycles. The formation of new follicles during the hair growth cycle is considered important to hair growth, at which time dermal papilla cells play a major role in follicle epithelial cell growth and differentiation as well as hair formation (Non-Patent Document 6). Extracts of astragalus root, Coptidis rhizome, and Wedelia chinensis are known examples of conventional drugs with action in stimulating dermal papilla cell growth, but there has yet to be provided a satisfactory hair growth agent that has action in stimulating dermal papilla cell growth, that has colored melanin-containing hair growth action, and that is free of side effects.
To deal with various types of external stress on the body (such as light, particularly UV rays, dust, exhaust gas, various chemical substances, and smoke) or bodily invasion by parasites or microbes such as viruses, bacteria, fungi, and protozoa, as well as antigen-induced allergic reactions, etc., these have conventionally been eradicated, or bactericides, fungicides, antibiotics, and the like have been used against microbes and parasites, and antibodies have been produced to develop resistance. However, until now, virtually no drugs have rehabilitated epithelial functions compromised by various external stimuli, by regenerating and stimulating the various epithelial functions which are most important in defending against external stimuli, microbial, parasitic, or other bodily invasion, and allergic responses, and which are the body's first inherent defense function against foreign threats. Furthermore, virtually no drugs rehabilitate epithelial functions by regenerating and stimulating the various epithelial functions that have become compromised as a result of aging. The inventor previously filed a patent application for a topical agent by the inventor which is applied to the skin to produce the four exceptional effects of making the skin smoother, healthier looking, fairer, and less wrinkled or unwrinkled with a single agent, as well as effects against atopic dermatitis. The topical agent by the inventor is furthermore effective against senile xerosis, frostbite, and housewives' eczema. Although the details of the mechanism involved in such effects remains unknown, the topical agent by the inventor may involve the effect of rehabilitating skin through the regeneration and stimulation of dermatological functions. Good therapeutic effects were found as a result of research on what kind of effect topical agents based on coenzyme Q10, cysteine, Vitamins A, C, and E, and an extract of inflamed skin from domestic rabbits inoculated with vaccinia virus, affording the beneficial effects on skin as noted above, would have on the epithelia of the ectodermal external auditory canal, nasal cavity, paranasal sinuses, oral cavity, and pharynx, on the epithelia of the endodermic tonsils, larynx, trachea, bronchi, and alveoli as well as mesodermic genital organs, which are all embryonically identical to skin, and also on hair, and what the effect would be when the epithelia of the above had aged and during pathological states. There is still a need for a drug that could be used over the long term to rehabilitate compromised epithelial functions through their regeneration and stimulation, and that could improve and rehabilitate aged or pathologically compromised epithelial functions.    [Patent Document 1] JP 2006-306832-A    [Patent Document 2] JP 2007-8815-A    [Patent Document 3] JP 2006-306813-A    [Patent Document 4] JP 2006-21997-A    [Patent Document 5] JP 11-228419-A    [Patent Document 6] JP 2000-86504-A    [Non-patent Document 1] M. Kylmaniemi, et al: J. Dent R s., 75, pp. 919-926 (1996)    [Non-patent Document 2] A. Haerian, et al: J. Clin Periodontol., 22 pp. 505-509 (1995)    [Non-patent Document 3] M. Makela, et a: J. Dent Res., 73, pp. 1397-1406 (1994)    [Non-patent Document 4] T. Nemoto, et al: Japanese Journal of Clinical and Experimental Medicine, vol. 54, 9 pp 3027-3029 (1977)    [Non-patent Document 5] Y. Sagawa, et al: The Japanese Journal of Chest Diseases, vol. 44, 9 pp 774-782 (1985)    [Non-patent Document 6] Trends Genet, 1992, vol. 8, pp 56-61